Carbon monoxide poisoning: a five year review at Tan Tock Seng Hospital, Singapore.

INTRODUCTION: Carbon monoxide poisoning (COP) is one of the leading causes of death from poisoning worldwide. There is no published study of COP in Singapore so far. MATERIALS AND METHODS: All patients admitted with the diagnosis of COP to Tan Tock Seng Hospital (TTSH) over 5 years from 1999 to 2003 were retrospectively reviewed. The diagnosis was based on a history of potential exposure to carbon monoxide (CO) and elevated levels of carboxyhaemoglobin (COHb). The causes, demographic data, clinical presentations, management and complications were analysed. RESULTS: There were 12 patients with COP. Their average age was 38.9 (+/-11.8) years, with a male-to-female ratio of 3:1. Accidental COP (58.3%) was more common than intentional COP (41.7%). The most common cause of accidental COP was smoke inhalation from a faulty vehicle. Gas stove was the most preferred source for intentional poisoning. Presenting features were headache (83.3%), confusion (83.3%), coma (12.7%) and agitation (8.3%). The mean COHb level on admission was 35.9% (+/-13.6). All were treated with 100% oxygen. All the patients achieved normal levels of COHb within 24 hours of admission. Two (16.7%) required intubation for airway protection as they were comatose on arrival, of which 1 presented with very high level of COHb (48.1%) and was the only patient to be treated with hyperbaric oxygen. Acute complications were globus pallidus infarction (16.6%), acute respiratory distress syndrome (8.3%) and myocardial ischaemia (8.3%). Most of the patients (91.7%) were discharged well from the hospital. One patient developed parkinsonism after a follow-up of 2 years. There were no deaths. CONCLUSION: COP is relatively uncommon in Singapore. It has a low rate of short- and long-term complications.

Severe adult chickenpox infection requiring intensive care.

INTRODUCTION: Chickenpox (varicella) in adults can be severe with increased mortality. This study investigated the clinical presentation and outcome of 12 adult chickenpox patients requiring intensive care. MATERIALS AND METHODS: A retrospective, observational study was performed in an adult medical intensive care unit of a university-affiliated hospital involving consecutive patients with varicella admitted over 4 years (1997-2000). RESULTS: The 12 patients had a mean +/- SD age of 40 +/- 20 (range, 15 to 86) years. Two patients were above 65 years old (aged 73 and 86 years). All but 1 were male. None had previous varicella vaccination. Six patients had direct exposure to persons with chickenpox infection. Four patients had underlying pulmonary pathology: past pulmonary tuberculosis (2), emphysema (1) and recurrent right pleural effusion from autoimmune serositis (1). The mean APACHE II score was 14.2 (range, 6 to 26). Ten patients had varicella pneumonia (of whom 2 had acute respiratory distress syndrome and 5 had acute lung injury), 1 had chickenpox encephalitis and 1 patient presented concomitantly with diabetic ketoacidosis. The median duration of stay in the intensive care unit (ICU) was 11 days (range, less than 1 day to 76 days). Nine patients (75%) required mechanical ventilation (median duration, 14 days; range, less than 1 day to 79 days). All patients were treated with acyclovir. There were 3 deaths (25%); 2 were above 65 years old and 1 was 37 years old with acute myeloid leukaemia on chemotherapy. CONCLUSION: Patients with varicella infection requiring intensive care carry significant mortality. In our series, old age appears to be associated with increased mortality (P = 0.045).

Radiographic features of a case of severe acute respiratory syndrome with fatal outcome.

INTRODUCTION: Severe acute respiratory syndrome (SARS) is a new form of atypical pneumonia caused by a coronavirus. We present the clinical course and chest radiographic findings of a case of SARS with fatal outcome. CLINICAL PICTURE: A 39-year-old Chinese male presented with fever, sore throat and non-productive cough. During his illness, serial chest radiographs showed increasingly severe air-space shadowing in both lungs. TREATMENT AND OUTCOME: The patient was treated with supplemental oxygen, levofloxacin, oseltamivir, ribavirin and methylprednisolone. As his condition worsened, the required ventilatory and inotropic support. He later developed a myocardial infarct and coagulopathy, and succumbed to his illness. CONCLUSION: The reported case mortality of SARS is about 9% worldwide. In Singapore, the mortality is 15.5%. Acute respiratory distress syndrome (ARDS) is believed to be a contributory factor to our patient's demise. We report this case to show the radiographic changes of ARDS in a patient with SARS.

Is increasing age associated with mortality in the critically ill elderly.

INTRODUCTION: Age has been cited as a predictor of mortality in the intensive care unit (ICU) and suggested as a criterion for rationing resources. We investigated the association of age with both ICU mortality and hospital mortality. MATERIALS AND METHODS: Patients admitted in 1998 to our Medical ICU (MICU) were retrospectively analysed by stratifying them into four groups: the reference group (55-64 years), the young old (65-74 years), the old old (75-84 years) and the oldest old (more than 85 years). The statistical association of age with ICU mortality and total hospital mortality was determined whilst controlling for the APACHE II(M) score (APACHE II score modified to exclude points for age), the number of organ failures and the presence of a high risk admitting diagnosis. RESULTS: After controlling for disease severity, the ICU mortality and the total hospital mortality were not associated with age. The total hospital mortality was associated with the APACHE II(M) score (Odds ratio (OR), 1.08; 95% Confidence intervals (CI), 1.04-1.12), the number of organ failures (OR, 2.03; CI, 1.50-2.67) and the presence of a high risk diagnosis (OR, 3.50; CI 1.93-6.37). The ICU mortality was also associated with the APACHE II(M) score (OR, 1.07; CI, 1.03-1.11), the number of organ failures (OR, 1.63; CI, 1.26-2.09) and the presence of a high risk diagnosis (OR, 3.22; CI 1.81-5.76). CONCLUSIONS: We did not find a statistically significant association between age and mortality. We recommend that age should not be used as a criterion for admission.

An audit of patients with rheumatic disease requiring medical intensive care.

INTRODUCTION: Medical intensive care for patients with rheumatic disease is usually complicated by significant morbidity and mortality. The aims of this study were to examine the reasons for admission, the outcomes of these patients and the possible prognostic factors in an Asian cohort. MATERIALS AND METHODS: This was a retrospective study of the case records of 29 admissions to the medical intensive care unit (MICU) of Tan Tock Seng Hospital (TTSH) from August 1999 to August 2000. RESULTS: There were 28 patients admitted, of whom 1 had a repeat admission. The majority of these patients were young (mean age 38.9 +/- 16.3 years) and 71.4% were females. Twenty patients (71.4%) had systemic lupus erythematosus (SLE). The main reasons for admission were infection/sepsis syndrome (n = 18), hypotension (n = 16) and acute respiratory failure (n = 14). The observed in-hospital mortality was 64.3%, which was higher than the predicted risk of hospital death of 47.3%. Infection contributed to 55.6% of deaths. The patients who died had a longer mean duration of the rheumatic disease, higher APACHE II scores, higher rates of hypertension and hyperlipidaemia, higher doses of steroid and immunosuppressive therapy and more organ failures. Renal failure and acute respiratory distress syndrome were the two most common organ failures in patients who died. CONCLUSION: Many of our critically-ill patients with rheumatic disease were young females with good functional status. Despite the high mortality, they should be aggressively treated because infection and acute respiratory failure are potentially reversible.

The practice of foregoing life support in the critically ill "old old": a Singapore perspective.

OBJECTIVE: To study the practice of foregoing life support (FLS) therapy between the young old and the old old. PATIENTS AND METHODS: This is a retrospective case-control study of case records for FLS events and illness characteristics among young old patients (55 to 74 years) and old old patients (75 years and older) admitted in 1998 to the medical intensive care unit (MICU). RESULTS: Fifty-seven out of 282 patients (20.2%) had FLS orders. There was no statistical difference in the use of FLS orders between the young old and the old old (17.1% versus 27.0%, P = 0.06), although there was a trend towards more frequent use in the old old. APACHE II(M) score (APACHE II score calculated without inclusion of points for age) and a high risk admitting diagnosis correctly predicted 80.5% of FLS events. A higher frequency of relatives of old old patients (20.8%) initiated FLS discussions compared to the young old (6%). In both groups, the child was the main surrogate decision-maker (n = 38, 66.7%). Medical futility/poor prognosis was the most common reason for FLS, accounting for 86.9% of patients. Withdrawing or withholding of mechanical ventilation was the most common mechanism (66.7%) of FLS. The majority (61.4%) died in the MICU after FLS. Of the 57 patients who had FLS orders, 1 young old and 3 old old survived till hospital discharge. CONCLUSION: Illness severity, as reflected by the APACHE II(M) score and the presence of a high-risk diagnosis, rather than age, predicted FLS orders.

Clinical features of patients with acute organophosphate poisoning requiring intensive care.

OBJECTIVES: To describe the clinical features of organophosphate poisoning (OPP), to evaluate the Acute Physiology and Chronic Health Evaluation (APACHE) II score as an alternative index for measuring OPP severity, and to assess cholinesterase levels for predicting successful weaning from mechanical ventilation (MV). DESIGN AND SETTING: Retrospective medical record review in a medical intensive care unit of an acute general hospital. PATIENTS: Twenty-three adults with OPP between 1995 and 1999. All cases were due to malathion poisoning. Muscarinic features were the predominant clinical manifestations (83%), followed by central nervous system (78%) and nicotinic manifestations (17%). RESULTS: MV was required by 74% of patients because of bronchial secretions (83%), altered conscious level (78%), pneumonia (78%), and flaccid paralysis (57%). Five patients (22%) had features of intermediate syndrome. ICU mortality was 13% and the mean ICU stay was 9.1 +/- 6.0 days. The mean APACHE II score was 17.4 +/- 7.4 and it correlated with mortality, severity of OPP, length of MV, and cholinesterase level. An APACHE II score of 26 or higher was predictive of mortality, with 95% sensitivity and 100% specificity. Threshold levels of serum and red blood cell cholinesterase for successful weaning from MV were 2,900 U/l and 7,500 U/l, respectively. CONCLUSIONS: The APACHE II score may be used as an alternative index of severity in patients with OPP; a score of 26 or higher is a good predictor of mortality. Cholinesterase levels are useful in predicting successful weaning of patients from MV.

A study of consecutive autopsies in a medical ICU : a comparison of clinical cause of death and autopsy diagnosis.

OBJECTIVE: To determine the degree of concordance between clinical cause of death and autopsy diagnosis in a medical ICU (MICU) setting. DESIGN: Retrospective medical chart and autopsy report review. SETTING: MICU in a tertiary referral hospital. PATIENTS: Consecutive admissions to an MICU over a 2-year period from January 1, 1994, to December 31, 1995. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand eight hundred patients were admitted to the MICU during the study period. There were 401 in-ICU deaths (22.3%). The autopsy rate was 22.7% (91 of 401). The mean +/- SD age of the autopsied patients (55.1 +/- 13.5 years) was lower than those without autopsy (62.4 +/- 15.2 years; p < 0.001). The two groups were otherwise similar with regard to sex, race, APACHE (acute physiology and chronic health evaluation) III scores, and lengths of stay in the MICU and hospital. The discordance between clinical and postmortem diagnoses was 19.8% (95% confidence interval, 12 to 29%). There were no differences in age, sex, APACHE III scores, predicted mortality, and lengths of stay in MICU hospital between patients with concordant and discordant diagnoses. In 44.4% (8 of 18) of the discordant cases, management would have been modified had the autopsied diagnosis been made premortem. Seven of the autopsied patients had organ transplantation. Three of the patients who had organ transplantation had discordant diagnoses, including two patients with disseminated fungal infection that was not diagnosed clinically. Although the observed discordance in transplant patients (43%) was higher than in those without transplant (19%), the difference was not statistically significant (p = 0.15). CONCLUSION: Younger patients tended to have a higher autopsy rate than older patients. The discordance between the clinical cause of death and postmortem diagnosis was 19.8%. In 44.4% of the discordant cases, knowledge of the correct diagnosis would have altered therapy.

Linkage and mutation analysis in two Taiwanese families with long QT syndrome.

Long QT syndrome (LQT) is a cardiovascular disorder causing syncope and sudden death from arrhythmias. Mutations in KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A genes encoding cardiac potassium and sodium ion channels cause LQT. Two Taiwanese LQT families were screened for mutations in these ion channel genes. In family H87, the diagnosis was made in the 25-year-old female proband and six family members based on recurrent syncope and/or a prolonged QT interval. Genotyping revealed a novel nonsense mutation, R744X (C to T transition in codon 744), in the KCNH2 potassium channel gene, resulting in truncation of the putative cyclic nucleotide-binding domain and C-terminal region of the HERG K(+)-channel in all affected family members. The mutation was confirmed by DdeI endonuclease digestion of the DNA from each family member. The 26-year-old female proband in family L89 developed repeated syncope with QTc of 0.61 seconds. After linkage and mutation analysis, the syndrome in this family was associated with a novel KCNQ1 missense mutation, T309I, causing the substitution of a threonine residue at position 309, in the pore region of the KvLQT1 K(+)-channel, with an isoleucine. By Tsp45I restriction analysis, the mutation was noted in the proband and the proband's asymptomatic brother, but was not detected in 100 unrelated normal individuals. Identification of a mutation has clinical implications for presymptomatic diagnosis and therapy.

Familial defective apolipoprotein B-100: detection and haplotype analysis of the Arg(3500)-->Gln mutation in hyperlipidemic Chinese.

Familial defective apolipoprotein (apo) B-100 (FDB) is caused by R3500Q mutation of the apo B gene resulting in decreased binding of LDL to the LDL receptor. Two other apo B mutations, R3500W and R3531C, affecting binding are known to date. We screened the apo B gene segment around codon 3500 by heteroduplex analysis and single strand conformation polymorphism (SSCP) analysis in a total of 373 hyperlipidemic individuals. Two single-base mutations were detected and confirmed by DNA sequencing. One mutation, ACA(3528)-->ACG change, resulted in degenerate codon with no amino acid substitution. The other mutation, CGG(3500)-->CAG mutation, resulted in an Arg(3500)-->Gln substitution (R3500Q). The prevalence of heterozygote in this selected population was 0.3% (95% confidence interval, 0.01-1.5%) for the R3500Q mutation, and 2.4% (95% confidence interval, 1.1-4.5%) for the previously described R3500W mutation. The results suggest that the R3500Q mutation is not a significant factor contributing to moderate hypercholesterolemia in Chinese (P=0.027). Family studies of the R3500Q carrier revealed a further two individuals heterozygous for the mutation, both of whom were hypercholesterolemic. Analysis of the R3500Q allele using six diallelic markers and the 3'HVR marker revealed a haplotype which was the same as that reported in a Chinese American but differed from that reported in a Chinese Canadian. Our data support limited multiple recurrent origins for R3500Q in Chinese population.

Romano-Ward long QT syndrome: identification of a HERG mutation in a Taiwanese kindred.

Romano-Ward syndrome is an autosomal dominant long-QT syndrome (LQTS) that predisposes affected individuals to sudden death from tachyarrhythmias. We investigated the molecular basis of LQTS in a Taiwanese kindred. Clinical and genetic analyses revealed that a mutation was linked to the human ether-a-go-go-related gene (HERG). The coding sequences and exon-intron borders of HERG were amplified by means of polymerase chain reaction and subjected to single-strand conformation polymorphism (SSCP) analysis. An exon with an aberrant SSCP pattern was cloned and sequenced to study the molecular lesion. A C-->T transition in codon 614, leading to substitution of a valine for an alanine residue in the pore region of the HERG protein, was identified. Analysis with Bsp12861 endonuclease digestion showed the mutation to be present in all affected family members. Given that an unaffected paternal uncle had inherited the same allele from the grandfather as the proband's father, a de novo mutation had apparently occurred in the father and was transmitted to his offspring. In addition to offering presymptomatic genetic diagnosis, identification of the disease-causing mutation may suggest new therapeutic approaches for treatment and prevention of this cardiovascular disease.

The natural history of dengue illness based on a study of hospitalised patients in Singapore.

AIM OF STUDY: To study the clinical features of dengue illness in hospitalised patients in Singapore. METHODS: One-hundred and thirty hospitalised patients with serologically confirmed dengue illness, from 1 April 1992 to 31 October 1992, were analysed retrospectively. RESULTS: Teenagers and young adults between 15 to 30 years of age were most commonly affected. The male to female ratio was 1.3:1. The mean duration of fever and rash prior to admission were 5.2 +/- 1.5 (mean +/- SD) days and 1.7 +/- 1.7 days respectively. Petechiae were present in 52.3% of the patients. Three-quarters of the patients with petechiae had platelet counts (PCs) of 100 x 10(3) ul-1 or less. Thrombocytopenia (PCs of 100 x 10(3) ul-1 or less) was first documented 5.8 +/- 1.4 days after the onset of illness. The nadir of thrombocytopenia occurred on the 6.4 +/- 1.6 day of illness. The mean duration of thrombocytopenia was 3.6 +/- 1.6 days. Nineteen patients (14.6%) had non life-threatening clinical bleeding or coagulopathy, namely bleeding gums (9 patients), epistaxis (5), vaginal spotting/menorrhagia (4) and prolonged PTT (3). Six patients (4.6%) required platelet transfusion because of severe thrombocytopenia (PCs less than 30 x 10(3) ul-1) and clinical bleeding. There was no secondary fall in the PCs over 2 or more consecutive days when the PCs were in the recovery phase. It took 1 more day to reach PCs of 100 x 10(3) ul-1, the "safe" level commonly used in Singapore to decide discharge of patients, as compared to 80 x 10(3) ul-1. At PCs of 80 x 10(3) ul-1 or more, 2 patients had bleeding gums, 1 each had epistaxis and vaginal spotting. No transfusion was required for these 4 patients. The mean hospital stay was 4.2 +/- 1.5 days. There was no mortality in this study. CONCLUSION: Dengue illness is a relatively benign self-limiting illness. When the PCs are on the rising trend and in the absence of clinical bleeding, it is reasonably safe to discharge patients when the PCs reach 80 x 10(3) ul-1, instead of 100 x 10(3) ul-1. This will shorten each patient's stay by 1 day, resulting in cost saving and more efficient use of hospital beds.

Human apolipoprotein E: correlation of polymorphisms and serum lipid concentrations in Chinese.

BACKGROUND: The allelic variation of the apolipoprotein E (apoE) gene affects serum lipid concentrations. This study investigates the correlation of apoE polymorphisms and serum cholesterol and triglyceride concentrations in Chinese subjects. METHODS: DNA from a random sample of 136 unrelated individuals was used for polymerase chain reaction (PCR) amplification of the three apoE alleles. The amplified products were analyzed by Hha1 restriction fragment length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP). RESULTS: Identical genotypes were obtained by both methods in all individuals analyzed. The three apoE alleles examined were in Hardy-Weinberg equilibrium (p = 0.417). The allele frequencies in individuals with cholesterol and triglyceride values of below 200 mg/dl were 8.6% for epsilon 2, 82.8% for epsilon 3 and 8.6% for epsilon 4. When allele frequency between individuals with cholesterol values of below and above 200 mg/dl was compared, there appeared little difference in the epsilon 2 and epsilon 4 alleles between the two groups (p = 0.823). Conversely, a statistically significant difference in the epsilon 2 allele was observed (p = 0.048) between individuals with triglyceride values of below and above 200 mg/dl. CONCLUSIONS: The results demonstrate that neither the epsilon 2 nor epsilon 4 alleles affect cholesterol values in Chinese subjects, whereas the epsilon 2 allele exerts an influence on serum triglyceride concentrations in Chinese.

Bronchoscopy in the intensive care unit (ICU).

The diagnostic and therapeutic utility of flexible fibreoptic bronchoscopy (FFB), coupled with its minimal morbidity and mortality, have led to its increasing use in the care of the critically ill patients. FFB allows direct inspection of the upper and lower airway, and facilitates the diagnosis and management of a variety of pulmonary disorders. Patients in the intensive care unit are predisposed to a higher risk of complications as they are usually mechanically ventilated with positive end-expiratory pressure, and have other medical conditions such as coagulopathies, thrombocytopenia, uraemia, cardiac disease, hypoxaemia, pulmonary hypertension, and immunosuppression. An awareness of the higher risks associated with certain clinical conditions, and an understanding of the pathophysiological consequences associated with FFB should alert the bronchoscopists to take the necessary precautions to prevent and deal with these problems.

Impact on quality of patient care and procedure use in the medical intensive care unit (MICU) following reorganisation.

We conducted this retrospective, cohort study to evaluate the quality of patient care and procedure use in the medical care unit (MICU) following reorganisation and staffing by an intensivist. Consecutive admissions to an adult MICU in a university affiliated hospital during two 3-month periods, August to October 1993 (Period 1, n = 112) and January to March 1994 (Period 2, n = 127) were analysed. In Period 1, the MICU was run under the open system in which patient care was provided by the individual attending physicians. In Period 2, a resident MICU team led by a trained intensivist took over the medical care from the primary physicians when the patients were admitted to the MICU. The intensivist also vetted MICU admission and decided on MICU discharge. In addition, there was a resident respiratory therapist to attend to ventilatory care during office hours. After office hours, the care of the MICU was delegated to the on-call team on a rotational basis among the medical departments. This was the semi-closed ICU model. The patients in the two periods were similar with respect to age, sex, race, source of admission and APACHE II scores. There was improvement in the median ICU length of stay for survivors from 3 days in Period 1, to 2 days in Period 2 (P = 0.0114). The relative risk of ICU death in Period 1 compared to Period 2 was 1.23 (P = 0.286). There was no significant difference in the use of peritoneal dialysis (5.4% versus 6.3%) and mechanical ventilation (55.4% versus 49.6%). However, utilisation of intra-arterial lines and pulmonary artery catheters increased from 0% in both Periods 1 and 2 to 23.6% and 5.5%, respectively. Reorganisation of the MICU in Period 2 resulted in reduced length of MICU stay for survivors. Hence, we believe that coverage by a dedicated ICU team and active respiratory care by a respiratory therapist during office hours were beneficial for the care of the critically ill. There was also a noticeable increase in the use of invasive monitoring.

Patients admitted to an intensive care unit for poisoning.

This paper presents our experience with patients admitted for poisoning to the adult medical intensive care unit (MICU), Tan Tock Seng Hospital, from 1 January 1993 to 31 December 1995. Case records of 50 consecutive patients admitted to the MICU for management of poisoning were retrospectively analysed for epidemiologic data and intensive care interventions. There were equal proportions of male and female patients. The majority (76%) were in the economically productive age group of 21 to 60 years old. Most patients (24 out of 50) stayed for 1 day only. The most common drugs involved were organophosphates and carbamates (16 occurrences), benzodiazepines (12 occurrences), tricyclic antidepressants (12 occurrences), and phenothiazines (8 occurrences). About a third involved multiple-agent poisoning; this was significantly more common in males. Fifty-eight per cent of patients had suicidal intent. There were 4 deaths (8%) during this period; 3 of these were due to poisoning by organophosphates and carbamates. Seventeen patients were ventilated, 2 underwent peritoneal dialysis, and 1 underwent forced diuresis.

Foregoing life support in medically futile patients.

Advances in medical technology have rendered the ability to provide prolonged physiologic support of incurable or terminally ill patients commonplace in the intensive care unit. In tandem, there has been a global shift in the intensivist's mindset from solely pursuing an unrelenting course of aggressive therapy, to a recognition of the limitations of intensive care and the appropriate discontinuance of nonbeneficial therapy. Underpinning this shift remains the physician's adherence to the ethical principles of beneficence, nonmaleficence, and disclosure; the patient's right to autonomy and self determination; and the community's right to just distribution of medical resources. When the doctor assumes the role of patient advocate, and assesses illness severity and evaluate recovery, or lack of, to a quality consistent with the patient's own life philosophy, he is able to communicate to the family a course of action that is in the patient's best interest. A consensus on withholding or withdrawal of care is often then achieved. The process of foregoing or withdrawing life-sustaining therapy itself, must be carried out with sensitivity and empathy, with the primary goal of providing comfort and reducing suffering.